DESCRIPTION: (verbatim) Numerous studies have indicated that the biomaterial scaffold architecture can significantly influence the outcome of tissue engineering treatments through effects on vascularization, tissue ingrowth and final tissue structure function. The ability to precisely design and manufacture biomaterial scaffolds would enhance understanding of how scaffolds influence tissue regeneration and lead to optimized biomaterial scaffolds for tissue engineering. We have recently developed image based computational techniques for designing and manufacturing hydroxyapatite ceramic scaffolds with specific complex internal microstructure and external shape. A preliminary study is to perform a more rigorous investigation into how scaffold design influences vascularization, tissue ingrowth, and tissue function in a minipig mandible model. The present study has three specific aims: Specific Aim 1: Verify that scaffold architecture influences early vascularization and tissue matrix deposition Specific Aim 2: Verify that scaffold architecture influences long-term bone structure and mechanical stiffness Specific Aim 3: Verify that early vascularization and mineralization lead to long-term bone formation and sufficient mechanical stiffness Three scaffold designs, an orthogonal circular strut, an orthogonal circular pore, and an orthogonal triangular pore, will be constructed at three different diameters from hydroxyapatite (HA) (3 designs x 3 perturbations = 9 different scaffolds). These scaffolds will be used to test our specific aims in the minipig mandible model. Animals will be sacrificed at 2 and 6 weeks to examine the short-term effects of internal scaffold architecture on cell differentiation and tissue deposition. Animals will be sacrificed at 18 and 52 weeks to examine long-term internal scaffold architecture influence on tissue structure and mechanical function. Results from this study will assist us in optimizing biomaterial scaffold performance via computational design to enhance regenerate tissue structure and function via tissue engineering treatments.